[gmx-users] free energy: annihilation

David Mobley dmobley at gmail.com
Tue Aug 29 18:16:34 CEST 2006


> > Yuguang reminds me of something else... I just did a bunch of
> > hydration free energy calculations for a large set of small molecules.
> > These tend to be pretty accurate for stuff that is mostly nonpolar,
> > but the larger the charges are, the bigger the deviation from
> > experiment can be. In particular, I tested a bunch of different charge
> > models; the average error is correlated with the dipole moment, among
> > other things. Generally, I would say that the larger your hydration
> > free energies are, the worse you will probably do compared to
> > experiment, unless you have some way of getting really terrific
> > partial charges or something. If DMSO has high partial charges, it
> > seems quite possible that the "right" answer for the hydration free
> > energy with those partial charges may end up being quite different
> > from experiment.
> >
> This seems weird, the only physical reason I can think of would be a
> contribution due to depolarization (as in Berendsen's SPC/E model). For
> water this would be roughly 4 kJ/mol. However for DMSO in my case it
> would be less, since it has a high dipole in the gas phase as well.
> Obviously if the model is poor results will be poor.

No, not systematic. Just think of it this way: If you have only small
partial charges, the only thing that can possibly  be wrong that will
make much difference is the LJ parameters or the water model. If the
partial charges are larger, they can also make a big difference in the
hydration free energy. Thus, for mostly apolar molecules, you can't do
*too* badly, since water molecules and LJ parameters are generally
decent. But for polar molecules, if your partial charges are really
bad, you can do very badly.

In other words, all I'm saying is basically that the larger the
hydration free energy is, the more wrong it can, which is fairly
obvious. :)

I actually found that, for my test set, depending on the partial
charges I used, I could get hydration free energies for polar
molecules that varied by more than a factor of 2. And these were all
"sensible" charge sets in some sense (QM-based, fit using RESP).

The moral of the story is that basically you should be careful what
charges you use, and be aware that it is possible for the charge set
to mess things up a whole lot.


> Could there be some other systematic problem?
> --
> David.
> ________________________________________________________________________
> David van der Spoel, PhD, Assoc. Prof., Molecular Biophysics group,
> Dept. of Cell and Molecular Biology, Uppsala University.
> Husargatan 3, Box 596,          75124 Uppsala, Sweden
> phone:  46 18 471 4205          fax: 46 18 511 755
> spoel at xray.bmc.uu.se    spoel at gromacs.org   http://folding.bmc.uu.se
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